Positron emission tomography (PET) imaging of tumor-localized Salmonella expressing HSV1-TK

Cancer Gene Ther. 2005 Jan;12(1):101-8. doi: 10.1038/sj.cgt.7700779.


In order to noninvasively detect Salmonella delivery vectors within tumors, we used a genetically modified Salmonella, VNP20009, that expresses the herpes simplex thymidine kinase (HSV1-tk) reporter gene. VNP20009-TK were able to selectively localize within murine tumor models and to effectively sequester a radiolabeled nucleoside analogue, 2'-fluoro-1-beta-D-arabino-furanosyl-5-iodo-uracil (FIAU). A quantitative relationship between the level of radioactivity accumulated and the number of bacteria in tumor and different tissues was demonstrated. The in vivo accumulation of [14C]FIAU measured in tissue sample homogenates and sections were related to Salmonella number and to immunohistochemical bacterial staining, respectively. Quantitative autoradiography (QAR) revealed the relative intensity of [14C]FIAU accumulation in a tumor cross-section, demonstrating that the peripheral region of the tumor was significantly less active than internal regions. [124I]FIAU positron emission tomography (PET) and subsequent tissue radioactivity and bacterial concentration measurements were compared. A log-log relationship was found, and the PET images could identify multiple tumor sites. The ability to noninvasively detect Salmonella vectors by PET imaging has the potential to be conducted in a clinical setting, and could aid in development of these vectors by demonstrating the efficiency and duration of targeting as well as indicating the locations of tumors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoradiography
  • Bacterial Vaccines
  • Carcinoma / genetics
  • Carcinoma / microbiology
  • Carcinoma / pathology
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / microbiology
  • Colonic Neoplasms / pathology
  • Disease Models, Animal
  • Genes, Reporter*
  • Genetic Vectors
  • Herpesvirus 1, Human / enzymology*
  • Humans
  • Immunohistochemistry
  • Melanoma / genetics
  • Melanoma / microbiology
  • Melanoma / pathology
  • Mice
  • Mice, Inbred C57BL
  • Positron-Emission Tomography*
  • Salmonella / genetics*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / microbiology
  • Skin Neoplasms / pathology
  • Thymidine Kinase / biosynthesis
  • Thymidine Kinase / genetics*
  • Vaccines, Attenuated


  • Bacterial Vaccines
  • VNP 20009
  • Vaccines, Attenuated
  • Thymidine Kinase